IRON OVERLOAD ALTERS INNATE AND T-HELPER CELL RESPONSES TO CANDIDA-ALBICANS IN MICE

The effect of iron overload on susceptibility of mice to Candida albic ans infection and on the type of T helper (Th) immunity elicited was i nvestigated, Iron overload greatly increased susceptibility to dissemi nated infection with low-virulence C. albicans cells of exogenous orig in, The candidacidal activity and the ability to release nitric oxide and bioactive interleukin (IL)-12 were greatly impaired in neutrophils and macrophages from infected mice. CD4 T cells from spleens of iron- overloaded mice were found to produce high levels of IL-4 and IL-10 an d low levels of interferon-gamma, Treatment of iron-overloaded mice wi th the iron chelator, deferoxamine, resulted in the cure of mice from infection, restored the antifungal effector and immunomodulatory funct ions of the phagocytic cells, and allowed the occurrence of CD4 Th1 pr otective antifungal responses, These data indicate that iron overload may negatively affect CD4 Th1 development in mice with candidiasis, a function efficiently restored by therapy with deferoxamine.